Effect of a patient-centered hypertension delivery strategy on all-cause mortality: Secondary analysis of SEARCH, a community-randomized trial in rural Kenya and Uganda.

BACKGROUND: Hypertension treatment reduces morbidity and mortality yet has not been broadly implemented in many low-resource settings, including sub-Saharan Africa (SSA). We hypothesized that a patient-centered integrated chronic disease model that included hypertension treatment and leveraged the HIV care system would reduce mortality among adults with uncontrolled hypertension in rural Kenya and Uganda. METHODS AND FINDINGS: This is a secondary analysis of the SEARCH trial (NCT:01864603), in which 32 communities underwent baseline population-based multidisease testing, including hypertension screening, and were randomized to standard country-guided treatment or to a patient-centered integrated chronic care model including treatment for hypertension, diabetes, and HIV. Patient-centered care included on-site introduction to clinic staff at screening, nursing triage to expedite visits, reduced visit frequency, flexible clinic hours, and a welcoming clinic environment. The analytic population included nonpregnant adults (≥18 years) with baseline uncontrolled hypertension (blood pressure ≥140/90 mm Hg). The primary outcome was 3-year all-cause mortality with comprehensive population-level assessment. Secondary outcomes included hypertension control assessed at a population level at year 3 (defined per country guidelines as at least 1 blood pressure measure <140/90 mm Hg on 3 repeated measures). Between-arm comparisons used cluster-level targeted maximum likelihood estimation. Among 86,078 adults screened at study baseline (June 2013 to July 2014), 10,928 (13%) had uncontrolled hypertension. Median age was 53 years (25th to 75th percentile 40 to 66); 6,058 (55%) were female; 677 (6%) were HIV infected; and 477 (4%) had diabetes mellitus. Overall, 174 participants (3.2%) in the intervention group and 225 participants (4.1%) in the control group died during 3 years of follow-up (adjusted relative risk (aRR) 0.79, 95% confidence interval (CI) 0.64 to 0.97, p = 0.028). Among those with baseline grade 3 hypertension (≥180/110 mm Hg), 22 (4.9%) in the intervention group and 42 (7.9%) in the control group died during 3 years of follow-up (aRR 0.62, 95% CI 0.39 to 0.97, p = 0.038). Estimated population-level hypertension control at year 3 was 53% in intervention and 44% in control communities (aRR 1.22, 95% CI 1.12 to 1.33, p < 0.001). Study limitations include inability to identify specific causes of death and control conditions that exceeded current standard hypertension care. CONCLUSIONS: In this cluster randomized comparison where both arms received population-level hypertension screening, implementation of a patient-centered hypertension care model was associated with a 21% reduction in all-cause mortality and a 22% improvement in hypertension control compared to standard care among adults with baseline uncontrolled hypertension. Patient-centered chronic care programs for HIV can be leveraged to reduce the overall burden of cardiovascular mortality in SSA. TRIAL REGISTRATION: ClinicalTrials.gov NCT01864603.

Household food insecurity, maternal nutritional status, and infant feeding practices among HIV-infected Ugandan women receiving combination antiretroviral therapy.

Household food insecurity (HHFI) may be a barrier to both optimal maternal nutritional status and infant feeding practices, but few studies have tested this relationship quantitatively, and never among HIV-infected individuals. We therefore described the prevalence of HHFI and explored if it was associated with poorer maternal nutritional status, shorter duration of exclusive breastfeeding (EBF) and fewer animal-source complementary foods. We assessed these outcomes using bivariate and multivariate analyses among 178 HIV-infected pregnant and breastfeeding (BF) women receiving combination antiretroviral therapy in the PROMOTE trial (NCT00993031), a prospective, longitudinal cohort study in Tororo, Uganda. HHFI was common; the prevalence of severe, moderate, and little to no household hunger was 7.3, 39.9, and 52.8 %, respectively. Poor maternal nutritional status was common and women in households experiencing moderate to severe household hunger (MSHH) had statistically significantly lower body mass index (BMIs) at enrollment (21.3 vs. 22.5, p < 0.01) and prior to delivery (22.6 vs. 23.8, p < 0.01). BMI across time during pregnancy, but not gestational weight gain, was significantly lower for MSHH [adjusted beta (95 % CI) -0.79 (-1.56, -0.02), p = 0.04; -2.06 (-4.31, 0.19), p = 0.07], respectively. The prevalence (95 % CI) of EBF at 6 months was 67.2 % (59.7-73.5 %), and the proportion of women BF at 12 months was 80.4 % (73.3-85.7 %). MSHH was not associated with prevalence of EBF at 6 months or BF at 12 months. However, among those women still EBF at 4 months (81.4 % of population), those experiencing MSHH were significantly more likely to cease EBF between 4 and 6 months (aHR 2.38, 95 % CI 1.02-5.58). The prevalence of HHFI, maternal malnutrition, and suboptimal infant feeding practices are high and the causal relationships among these phenomena must be further explored.

Early virologic failure and the development of antiretroviral drug resistance mutations in HIV-infected Ugandan children.

BACKGROUND: Without virologic testing, HIV-infected African children starting antiretroviral (ARV) therapy are at risk for undetected virologic failure and the development of ARV resistance. We sought to determine the prevalence of early virologic failure (EVF), to characterize the evolution of ARV-resistance mutations and to predict the impact on second-line therapy. METHODS: The prevalence of EVF (HIV RNA >400 copies/mL on sequential visits after 6 months of therapy) was identified among 120 HIV-infected Ugandan children starting ARV therapy. ARV mutations were identified by population sequencing of HIV-1 pol in sequential archived specimens. Composite discrete genotypic susceptibility scores were determined for second-line ARV regimens. RESULTS: EVF occurred in 16 children (13%) and persisted throughout a median (interquartile ratio) 938 (760-1066) days of follow-up. M184V and nonnucleoside reverse transcriptase inhibitor-associated mutations emerged within 6 months of EVF; thymidine-analog-mutations arose after 12 months. Worse discrete genotypic susceptibility scores correlated with increasing duration of failure (Spearman R = -0.47; P = 0.001). Only 1 child met World Health Organization CD4 criteria for ARV failure at the time of EVF or during the follow-up period. CONCLUSIONS: A significant portion of HIV-infected African children experience EVF that would be undetected using CD4/clinical monitoring and resulted in the accumulation of ARV mutations that could compromise second-line therapy options.

Inappropriate antibiotic use in soft tissue infections.

HYPOTHESIS: Many soft tissue infections treated with surgical drainage resolve even when treated with antibiotics not active against the organism isolated from the infection. DESIGN: Retrospective. SETTING: Integrated Soft Tissue Infection Services clinic. PATIENTS: All patients treated from July 19, 2000, to August 1, 2001, who underwent surgical drainage of a soft tissue infection and had microbiological culture results. MAIN OUTCOME MEASURES: Documented resolution of the infection with drainage of the abscess and antibiotic therapy alone was deemed a cure. An infection resulting in death or other surgical therapy was deemed a failure. Therapy was appropriate when the organism was sensitive to prescribed antibiotics and was inappropriate when the organism was insensitive. RESULTS: The study included 376 patients with 450 infections. Staphylococcus aureus as the primary organism was isolated from 441 of the cultures. Methicillin sodium-sensitive S aureus and methicillin-resistant S aureus were found in 157 and 284 of these isolates, respectively. Appropriate antibiotics were prescribed in 153 infections with methicillin-sensitive S aureus and in 25 with methicillin-resistant S aureus. Of 441 episodes, 408 were clinically evaluated for cure. Three patients failed treatment, 2 in the appropriately treated group (resulting in death and amputation) and 1 patient with osteomyelitis in the inappropriately treated group. The cure rate for infections treated appropriately or inappropriately was the same. CONCLUSIONS: Treatment of soft tissue infections after surgical drainage, even with inappropriate antibiotics, has a high cure rate. Further studies to evaluate the efficacy of treating these infections without antibiotics are needed.